Factors controlling the activity of HMG-CoA reductase, the key regulatory enzyme of sterol biosynthesis, are being examined along the following general lines of investigation. 1. The effect of lipid inhibitors such as oleic acid and oleoyl CoA on the conformation of the enzyme and the possible physiological role that these inhibitors may play in regulation of enzyme activity. In addition, the effect of substrates in preventing the above inhibition is being investigated from the viewpoint of alternatives of enzyme structure. The role that cholesterol esterases, phospholipases, and triglyceride lipase activity in the endoplasmic reticulum may play in generating the above mentioned inhibitors will also be investigated. 2. Phoshorylation and dephosphorylation of the enzyme in rat intestinal mucosal cells and the role that these processes play in the regulating of sterol synthesis in intestinal mucosal cells. 3. Production of antibody to the enzyme with the aim of developing a simple immunoassay procedure to determine variations in the level of enzyme protein in relation to changes in physiological regulation of HMG-CoA reductase activity. Also, the turnover time of the enzyme protein will be reinvestigated.